HYPOTHESIS: The overall goal of the proposed research is to identify regulatory factors affecting the transcription and expression of CYP3A4, which determine the interindividual variability in the enzyme's basal level of activity and its inducibility by xenobiotics. SPECIFIC AIMS: 1) To determine the effect of known allelic variants involved in CYP3A4 transcriptional control on the enzyme's basal and rifampin-induced in vivo catalytic activity in different populations. 2) To identify currently unknown genetic determinants of CYP3A4 activity by a genome-wide search using sib-pair analysis and to determine the mode of inheritance of functionally significant traits.